Warning! This synopsis may contain spoilers

Ten years after he defeated the Kraken, Perseus (Sam Worthington), the demigod son of Zeus (Liam Neeson), now lives as a fisherman with his 10-year-old son, Heleus (John Bell). One night, Perseus is visited by Zeus, who tells him that the powers of the gods are fading and the walls of the underworld prison of Tartarus are breaking due to the lack of devotion from humans and states they will need the world's armies to combat the potential threat, but Perseus shows little interest and refuses to get involved. Afterwards, Zeus travels to Tartarus to meet with his brothers Hades (Ralph Fiennes) and Poseidon (Danny Huston), and his son Ares (Edgar Ramirez). He tells Hades they must forget the past and unite to rebuild Tartarus, but Hades orders his minions to attack. They severely injure Poseidon, and Ares betrays Zeus over showing Perseus more affection, taking him prisoner and stealing his thunderbolt. Hades and Ares plan to drain Zeus' power to revive Kronos, the father of Zeus, Hades, and Poseidon, in exchange for the two to remain immortal. The walls of Tartarus break, unleashing monsters into the world.

After slaying a Chimera that attacks his village, Perseus takes Heleus to the Mount of Idols, so they can speak to Zeus, but the dying Poseidon arrives instead. He informs Perseus that Hades and Ares are holding Zeus in Tartarus, and tells him to meet with his demigod son Agenor (Toby Kebbell) to find the fallen god Hephaestus, who knows the way into Tartarus. Poseidon then gives Perseus his trident before succumbing to his injuries and crumbling into dust. Perseus flies on Pegasus to the campsite of Queen Andromeda's army. Andromeda (Rosamund Pike) has imprisoned Agenor for stealing crown jewels, but Perseus has him released.

Perseus, Andromeda, Agenor, and a group of soldiers set out at sea to find Hephaestus, with Agenor explaining that Hephaestus created the three great weapons that Zeus, Hades, and Poseidon wield: Zeus Thunderbolt, Hades' Pitchfork, and Poseidons Trident, and that together they form the Spear of Triam, the only weapon that can defeat Kronos. Agenor uses Poseidon's trident to direct the boat to Hephaestus's island, where they encounter three Cyclopes who attack them. When Perseus shows them the trident, they lead the group to Hephaestus (Bill Nighy), the smith god, stripped of much of his godly power after siding with Hades after he betrayed the Olympians ten years prior. He explains that he has a map to navigate the path into Tartarus. He leads them to the door into the Labyrinth, where they are attacked by Ares after Korrina prays to him. Ares kills most of the soldiers as well as Korrina while Hephaestus opens the door, before he sacrifices himself so that Perseus, Andromeda, and Agenor can enter the door before it closes.

Agenor tries to use the map to direct them, but the Labyrinth continually shifts and at one point nearly crushes them. Perseus gets cut off from the group and encounters and kills the Minotaur. Eventually, the group manages to reunite outside of Tartarus. Meanwhile, Zeus has been almost entirely drained of power as Kronos starts to awaken. Zeus apologizes to Hades and asks his forgiveness, as he has forgiven Hades for his actions. Hades has a change of heart and finally decides to help Zeus and stop Kronos, but Ares intervenes. Perseus arrives and uses the trident to free Zeus. As they are escaping, Ares throws Hades's pitchfork into Zeus's back. Perseus, Andromeda, Agenor and Hades carry a weakened Zeus down to the base of the mountain where Andromeda's army is gathered. Perseus combines the trident and Hades pitchfork, but he still needs Zeus's thunderbolt, which Ares still has, to complete the Spear. Perseus prays to Ares, challenging him to a fight at the Temple of Gods, which Ares accepts.

At the temple, Perseus finds out Ares has kidnapped Heleus, who was brought to watch Perseus die. Ares easily overpowers Perseus, but he is distracted when Heleus tries to challenge him by pointing a sword at him, giving Perseus the opportunity to defeat him. Perseus then destroys Ares with Zeus's Thunderbolt and combines the gods' weapons into the Spear of Triam. Meanwhile, Andromeda's army is overwhelmed by Kronos' army of Makhai, but Hades arrives to revive Zeus and together they use what power they have left to defeat the army, who have murdered most of Andromeda's men. Kronos then appears and begins to attack them, from which Zeus and Hades defend them and at the same time are giving Perseus the opportunity to fly right down Kronos' throat. Kronos lets out one last blast, and Zeus takes the brunt of the force to protect Hades. Perseus throws the Spear of Triam into Kronos' stomach, destroying him once and for all. Perseus meets with Zeus and Hades; Zeus commends Perseus for his courage, stating that the time of the gods is over before turning to dust. Hades is now mortal, though he states he might be better off as such before walking away. Perseus reunites with Andromeda and kisses her. Knowing that there are still Titans to battle, Perseus decides to train Heleus to be a soldier.